Major Organ Weights Research Articles

Co-delivery of Paclitaxel/Atovaquone/Quercetin to regulate energy metabolism to reverse multidrug resistance in ovarian cancer by PLGA-PEG nanoparticles

Ovarian cancer is a malignant tumor that seriously endangers the lives of women, with chemotherapy being the primary clinical treatment. However, chemotherapy encounters the problem of generating multidrug resistance (MDR), mainly due to drug efflux induced by P-glycoprotein (P-gp), which decreases intracellular accumulation of chemotherapeutic drugs. The drugs efflux mediated by P-gp requires adenosine triphosphate (ATP) hydrolysis to provide energy. Therefore, modulating energy metabolism pathways and inhibiting ATP production may be a potential strategy to reverse MDR. Herein, we developed a PTX-ATO-QUE nanoparticle (PAQNPs) based on a PLGA-PEG nanoplatform capable of loading the mitochondrial oxidative phosphorylation (OXPHOS) inhibitor atovaquone (ATO), the glycolysis inhibitor quercetin (QUE), and the chemotherapeutic drug paclitaxel (PTX) to reverse MDR by inhibiting energy metabolism through multiple pathways. Mechanistically, PAQNPs could effectively inhibit the OXPHOS and glycolytic pathways of A2780/Taxol cells by suppressing the activities of mitochondrial complex III and hexokinase II (HK II), respectively, ultimately decreasing intracellular ATP levels in tumor cells. Energy depletion can effectively inhibit cell proliferation and reduce P-gp activity, increasing the chemotherapeutic drug PTX accumulation in the cells. Moreover, intracellular reactive oxygen species (ROS) is increased with PTX accumulation and leads to chemotherapy-resistant cell apoptosis. Furthermore, PAQNPs significantly inhibited tumor growth in the A2780/Taxol tumor-bearing NCG mice model. Immunohistochemical (IHC) analysis of tumor tissues revealed that P-gp expression was suppressed, demonstrating that PAQNPs are effective in reversing MDR in tumors by inducing energy depletion. In addition, the safety study results, including blood biochemical indices, major organ weights, and H&E staining images, showed that PAQNPs have a favorable in vivo safety profile. In summary, the results suggest that the combined inhibition of the two energy pathways, OXPHOS and glycolysis, can enhance chemotherapy efficacy and reverse MDR in ovarian cancer.

Safety Evaluation of Amaranth Extract by Acute, Sub-Chronic and Chronic Exposure in Rats

Amaranth is one of the popularly grown leafy vegetables in tropical regions globally and contains a large amount of nitrate. The present study's objective was evaluation of acute and repeated dose toxicity of amaranth extract as per the OECD guidelines. The acute oral toxicity was conducted in 6 female rats (150-170 g; 8-10 Weeks old) as per OECD 423 guidelines. The amaranth extract had no adverse/toxic effects and no mortality was noted at the dose of 2000mg/kg. The oral LD50, therefore, was considered greater than 2000mg/kg. The sub-chronic (28-day repeated dose) toxicity was studied in 40 rats (150-170 g; 8-10 Weeks old) as per OECD 407 guidelines whereas chronic (365-days repeated dose) toxicity study was conducted in 200 rats (150-170 g; 8-10 Weeks old) as per OECD 452 guidelines. Sub-chronic study confirmed the safety of amaranth extract at the highest dose of 1000 mg/kg/day. The 1000 mg/kg in rats was considered as NOEL (No Observed Adverse Effect Level). The chronic toxicity study established a NOEL of 180 mg/kg in rats. In the repeated dose toxicity studies, body weight, food consumption, blood profile, biochemistry parameters and histopathology of major organs were similar in test and control groups. The current study results indicated that amaranth extract was safe upon acute, sub-chronic and chronic administration in rats, under testing conditions and at dose levels employed.

Evaluation of the Safety and Gastrointestinal Migration of Guanidinylated Chitosan after Oral Administration to Rats.

Arginine-rich membrane-permeable peptides (APPs) can be delivered to cells by forming complexes with various membrane-impermeable bioactive molecules such as proteins. We recently reported on the preparation of guanidinylated chitosan (GCS) that mimics arginine peptides, using chitosan, a naturally occurring cationic polysaccharide, and confirmed that it enhances protein permeability in an in vitro cell system. However, studies on the in vivo safety of GCS are not available. To address this, we evaluated the in vivo safety of GCS and its translocation into the gastrointestinal tract in rats after a single oral administration of an excessive dose (500 mg/kg) and observed changes in body weight, major organ weights, and organ tissue sections for periods of up to 2 weeks. The results indicated that GCS causes no deleterious effects. The results of an oral administration of rhodamine-labeled chitosan and an evaluation of its migration in the gastrointestinal tract suggested that the disappearance of rhodamine-labeled GCS from the body appeared to be slower than that of the non-dose group and pre-guanidinylated chitosan due to its mucoadhesive properties. In the future, we plan to investigate the use of GCS to improve absorption using Class III and IV drugs, which are poorly water-soluble as well as poorly membrane-permeable.

Rhesus macaque fetal and placental growth demographics: A resource for laboratory animal researchers.

Rhesus macaques (Macaca mulatta) are amongst the most common nonhuman primate species used in biomedical research. These animals provide a precious resource for translational studies and opportunities to maximize rhesus data use are encouraged. Here we compile data produced from 10 years of investigator-driven pregnancy studies conducted at the Oregon National Primate Research Center (ONPRC). All pregnancies were generated within the consistent and reproducible protocols of the ONPRC time-mated breeding program. The data included are from control animals who did not experience in utero perturbations or experimental manipulations. A total of 86pregnant rhesus macaques were delivered by cesarean section over a range of gestational days (G) 50 to G159 (where term is G165 ± 10 days in the rhesus macaque), with subsequent immediate tissue harvesting following standardized protocols. Fetal and placental growth measures, and all major organ weights are reported. All data are presented relative to gestational age for the entire cohort and in addition, data are stratified by fetal sex. The outcome is a large reference resource for use by laboratory animal researchers in future comparative fetal development studies.

Immune-Enhancing Effect of Sargassum horneri on Cyclophosphamide-Induced Immunosuppression in BALB/c Mice and Primary Cultured Splenocytes.

Sargassum horneri (SH) is a seaweed that has several features that benefit health. In this study, we investigated the immune-enhancing effect of SH, focusing on the role of spleen-mediated immune functions. Chromatographic analysis of SH identified six types of monosaccharide contents, including mannose, rhamnose glucose, galactose xylose and fucose. SH increased cell proliferation of primary cultured naïve splenocytes treated with or without cyclophosphamide (CPA), an immunosuppression agent. SH also reversed the CPA-induced decrease in Th1 cytokines. In vivo investigation revealed that SH administration can increase the tissue weight of major immune organs, such as the spleen and thymus. A similar effect was observed in CPA-injected immunosuppressed BALB/c mice. SH treatment increased the weight of the spleen and thymus, blood immune cell count and Th1 cytokine expression. Additionally, the YAC-1-targeting activities of natural killer cells, which are important in innate immunity, were upregulated upon SH treatment. Overall, our study demonstrates the immune-enhancing effect of SH, suggesting its potential as a medicinal or therapeutic agent for pathologic conditions involving immunosuppression.

HDAC inhibitor quisinostat prevents estrogen deficiency-induced bone loss by suppressing bone resorption and promoting bone formation in mice

Postmenopausal osteoporosis (PMOP) is a metabolic skeletal disorder characterized by reduced bone mass and impaired bone microarchitecture resulting in increased bone fragility and fracture risk. PMOP is primarily caused by excessive osteoclastogenesis induced by estrogen deficiency. Quisinostat (Qst) is a potent hydroxamate-based second-generation inhibitor of histone deacetylases (HDACs) that can inhibit osteoclast differentiation in vitro, and protect mice from titanium particle-induced osteolysis in vivo. However, whether Qst has therapeutic potential against PMOP remains unclear. In the present study, we evaluated the therapeutic efficacy of Qst on PMOP, using a murine model of ovariectomy (OVX)-induced osteoporosis. We examined the body weight, femur length, and histology of major organs, and showed that Qst did not cause obvious toxicity in mice. Micro-computed tomography and histological analyses revealed that Qst treatment prevented OVX-induced trabecular bone loss both in femurs and vertebrae. Moreover, ELISA showed that Qst decreased the serum levels of the osteoclastic bone resorption marker CTX-1, whereas increased the levels of the osteoblastic bone formation marker Osteocalcin in OVX mice. Consistent with the CTX-1 results, TRAP staining showed that Qst suppressed OVX-induced osteoclastogenesis. Mechanistically, we showed that Qst suppressed RANKL-induced osteoclast differentiation in part by inhibiting p65 nuclear translocation. Collectively, our results demonstrated that Qst can ameliorate estrogen deficiency-induced osteoporosis by inhibiting bone resorption and promoting bone formation in vivo. In summary, our study provided the first preclinical evidence to support Qst as a potential therapeutic agent for PMOP prevention and treatment.

Evaluating the biological safety on mice at 16 T static magnetic field with 700 MHz radio-frequency electromagnetic field

ObjectivesThis study evaluated the associated biological effects of radio-frequency (RF) exposure at 16 T magnetic resonance imaging (MRI) on mice health. Material and methodsA total of 48 healthy 8-week-old male C57BL/6 mice were investigated. A 16 T high static magnetic field (HiSMF) was generated by a superconducting magnet, and a radiofrequency (RF) electromagnetic field for hydrogen resonance at 16 T (700 MHz) was transmitted via a homemade RF system. The mice were exposed inside the 16 T HiSMF with the 700 MHz RF field for 60 min, and the body weight, organ coefficients, histomorphology of major organs, and blood indices were analyzed for the basal state of the mice on day 0 and day 14. The Heat Shock Protein 70 (HSP70), cyclooxygenase 2 (COX2), and interleukin- 6 (IL-6) were used to evaluate the thermal effects on the brain. Locomotor activity, the open field test, tail suspension test, forced swimming test, and grip strength test were used to assess the behavioral characteristics of the mice. ResultsThe 16 T HiSMF with 700 MHz RF electromagnetic field exposure had no significant effects on body weight, organ coefficients, or histomorphology of major organs in the mice. On day 0, the expressions of HSP70 and COX2 in the brain were increased by 16 T HiSMF with 700 MHz RF electromagnetic field exposure. However, the expression of HSP70, COX2, and IL-6 had no significant difference compared with the sham group on day 14. Compared with the sham groups, the meancorpuscularvolume (MCV) on day 0 and the total protein (TP) on day 14 were increased significantly, whereas the other blood indices did not change significantly. The 16 T HiSMF with 700 MHz RF electromagnetic field exposure caused the mice to briefly circle tightly but had no effect on other behavioral indicators. ConclusionsIn summary, 16 T HiSMF with 700 MHz RF electromagnetic field exposure for 60 min did not have severe effects on mice.

육계 사료 내 인삼 부산물 첨가 급여가 생산성, 장기 무게 및 혈액 생화학 특성에 미치는 영향

The aim of this study was to analyze the effect of dietary supplementation with ginseng berry, stems, and leaves on the growth performance, organ development, and blood biochemical characteristics of broilers. One hundred twenty one-day-old male broiler chicks (Ross 308) were randomly allocated to five groups: control (CON), ginseng berry 0.5% (GB1), ginseng berry 1.0% (GB2), ginseng stems and leaves 0.5% (GLS1), and ginseng stems and leaves 1.0% (GLS2). During the grower period (1–21 d), the body weight gain of all ginseng by-product fed groups was significantly higher (p<0.05) than that of the control group. During the finisher period (22–35 d), the feed intake in GLS2 was significantly higher (p<0.05) than that in the other groups, but there was no significant difference in weight gain or feed conversion ratio. No significant differences were detected among treatments when the growth performance was analyzed throughout the entire period (1–35 d). There was no significant difference in the serum biochemical profile, except for blood glucose. Glucose levels were significantly lower (p<0.05) in GLS groups, and tended to be lower in GB groups when compared to the control. Major organ weights showed no significant differences among treatment groups when compared to each other. In conclusion, dietary supplementation of ginseng by-products may improve the early growth of broiler chickens and reduce blood glucose levels.

Oral toxicity evaluation of gokshuradi guggulu, an ayurvedic formulation

Gokshuradi guggulu is an important classical polyherbal formulation used in Ayurvedic system of medicine for the treatment of various chronic diseases like kidney stones and diabetes. However, no scientific attempts were made to evaluate its oral toxicity. Hence, the present study evaluated the acute and 28 days repeated dose sub-acute oral toxicities of gokshuradi guggulu in rats. Gokshuradi guggulu was tested for its compliance using physicochemical and analytical parameters as per standards prescribed in Ayurvedic Pharmacopeia of India. In acute oral toxicity study, Wistar rats were orally administered a single dose of gokshuradi guggulu (2700 mg/kg) and clinical signs and mortality or moribund stage were observed for 14 days along with weekly body weight. On day 15, the rats were euthanized and the gross morphology was carried out during necropsy. In sub-acute (repeated dose) oral toxicity study, the rats were orally administered gokshuradi guggulu (270, 1350 and 2700 mg/kg) once daily up to 28 days. Clinical signs and mortality or moribund stage, weekly body weight, weekly feed and water consumptions, biochemical and hematological investigations, urine analysis, and major organ weights and histopathology were carried out. In acute and sub-acute toxicity studies, gokshuradi guggulu administration did not show any alteration in parameters or any adverse effect as compared to vehicle treated group. There was no mortality or moribund state observed in any group in both studies. Administration of gokshuradi guggulu in acute and 28 days repeated doses did not exhibit any toxicity or adverse effect at the doses used and NOAEL was found to be 2700 mg/kg.

Systematic evaluation of CdSe/ZnS quantum dots toxicity on the reproduction and offspring health in male BALB/c mice

Increased applications of quantum dots (QDs) in the biomedical field have aroused attention for their potential toxicological effects. Although numerous studies have been carried out on the toxicity of QDs, their effects on reproductive and development are still unclear. In this study, we systematically evaluated the male reproductive toxicity and developmental toxicity of CdSe/ZnS QDs in BALB/c mice. The male mice were injected intravenously with CdSe/ZnS QDs at the dosage of 2.5 mg/kg BW or 25 mg/kg BW, respectively, and the survival status, biodistribution of QDs in testes, serum sex hormone levels, histopathology, sperm motility and acrosome integrity was measured on Day 1, 7, 14, 28 and 42 after injection. On Day 35 after treatment, male mice were housed with non-exposed female mice, and then offspring number, body weight, organ index and histopathology of major organs, blood routine and biochemical tests of offspring were measured to evaluate the fertility and offspring health. The results showed that CdSe/ZnS QDs could rapidly distribute in the testis, and the fluorescence of QDs could still be detected on Day 42 post-injection. QDs had no adverse effect on the structure of testis and epididymis, but high-dose QDs could induce apoptosis of Leydig cells in testis at an early stage. No significant differences in survival of state, body weight organ index of testis and epididymis, sex hormones levels, sperm quality, sperm acrosome integrity and fertility of male mice were observed in QDs exposed groups. However, the development of offspring was obviously influenced, which was mainly manifested in the slow growth of offspring, changes in organ index of main organs, and the abnormality of liver and kidney function parameters. Our findings revealed that CdSe/ZnS QDs were able to cross the blood-testis barrier (BTB), produce no discernible toxic effects on the male reproductive system, but could affect the healthy growth of future generations to some extent. In view of the broad application prospect of QDs in biomedical fields, our findings might provide insight into the biological safety evaluation of the reproductive health of QDs.

Protein requirement of Japanese quail (coturnix corturnix japonica) chicks in Nigeria

A feeding trial was conducted to determine the effect of varying dietary levels of protein on performance of Japanese quail chicks. Six iso-caloric (2953-3078 kcal/kg, ME) diets were formulated to contain crude protein (CP) at 18, 20, 22, 24, 26 and 28% levels, respectively. Each of the dietary treatment was replicated three times with sixty (60) quail chicks per replicate. A total of 1080 day-old unsexed quail chicks were used for the study and distributed using completely randomized design. The experiment lasted 42 days during which data were collected. Feed and water were provided ad libitum throughout the experimental period. Feed intake, weight gain, feed conversion ratio and protein intake differ significantly (P<0.05) due to dietary treatments. Final live weight and cost per gain were not significantly (P>0.05) different across dietary treatments. Age at first egg and average weight of eggs at point of lay differed significantly (P<0.05) across dietary treatments. The haematological parameters (Total protein, haemoglobin, albumen and red blood cell) were significantly (P<0.05) affected by the dietary protein levels. Carcass weight, dressing percentage, prime cuts and the weight of major organs expressed as percentage of the live weight were not significantly (P>0.05) affected by the dietary treatments. It was concluded that Japanese quail chicks required up to 26% level of dietary protein for optimum performance.

Protein quality and safety evaluation of sarcoplasmic protein derived from silver carp (Hypophthalmichthys molitrix) using a rat model.

Consisting of 25 to 30% of protein in carp, water-soluble sarcoplasmic proteins lost in wash water, have been recovered and freeze-dried into a protein-rich powder. Study objectives were to evaluate protein quality and safety of a silver carp sarcoplasm derived protein powder (CSP) compared to commercial protein supplements, casein, and whey. In vivo protein quality assessment of CSP showed a lower (P<0.05) protein digestibility corrected amino acid score compared to the commercial protein sources. Despite greater (P<0.05) fecal amino acid excretion in casein-fed rats, there were no significant differences in liver and muscle amino acid profiles. All low (10%kcal) protein diets supported growth with the normal range. However, whey protein supplementation resulted in greater (P<0.05) adiposity. CSP, casein, or whey-fed rats showed no differences in major organ weights, renal damage biomarkers, or bone indices. Collectively, results indicated CSP was safe with protein quality comparable to casein. PRACTICAL APPLICATION: As much as 40 percent of protein in fish can be lost due to sarcoplasmic protein solubilization in processing wash water. Silver carp sarcoplasm protein powder may have similar commercial potential as a sustainable and nutritious alternative to whey and casein proteins. This project aimed to verify the protein quality and safety of this economical protein source.

Doxorubicin and CD‑CUR inclusion complex co‑loaded in thermosensitive hydrogel PLGA‑PEG‑PLGA localized administration for osteosarcoma.

Combination therapy is a promising and prevalent strategy for osteosarcoma treatment. Curcumin (CUR), as a chemosensitizer, improves the antitumor effect of first-line chemotherapy drugs. However, due to its poor solubility and instability in physiological conditions, the bioavailability of CUR is limited. In order to improve the physicochemical properties of natural CUR, β-cyclodextrin was adopted to generate a β-cyclodextrin curcumin (CD-CUR) inclusion complex. A thermosensitive hydrogel, poly(D,L-lactide-co-glycolide)-poly(ethylene-glycol)-poly(D,L-lactide-co-glycolide), was selected and synthesized to co-deliver doxorubicin (DOX) and CD-CUR to tumor sites. The dual-drug delivery system (gel+DOX+CD-CUR) was prepared by mixing drugs with hydrogels and had a perfect sol-gel phase transition temperature (18.3°C for 20% concentration). Both DOX and CUR were released from hydrogels in a sustained manner in PBS (pH 7.4) medium. The combination therapy based on DOX+CD-CUR exhibited higher antitumor activity than monotherapies in vitro. Combined CD-CUR therapy significantly downregulated Bcl-2 expression and upregulated caspase-3 expression, suggesting that DOX combined with CD-CUR treatment has a higher apoptosis-inducing efficiency. The antitumor efficiency of the gel+DOX+CD-CUR strategy was evaluated in K-7 tumor-bearing mice, and this localized combination therapy demonstrated a higher antitumor efficiency compared with free DOX+CD-CUR or single-drug strategies. There were no significant differences in body weight and histological changes of major organs in each group. Therefore, the present combination treatment based on hydrogel may be a feasible approach to co-deliver DOX and CD-CUR to osteosarcoma tumor sites in clinical practice.

Establishment of Reference Ranges for Normal Organ Weights in Malaysian Adults at Autopsy.

Organ weights are routinely measured during autopsies as a crude screening tool to detect possible organ pathology. In several centers, inclusion of major organ weights indicates whether an autopsy report has achieved its standard of practice, which in turn should be subjected to an audit. Previous studies show statistical variation in organ weights across different populations. Malaysian pathologists have relied on Western data and crude subjective determination in the interpretation of normal organ weights. Hence, the need for a reference range as a guide for pathologists is acute. Organ weights from traumatic deaths between 2004 and 2017 were analyzed in the UKM Medical Centre. Statistical analysis was performed to form reference ranges for normal weights of the brain, heart, lung, liver, spleen, and kidneys. In addition, the data were compared between sexes, races, and body mass index values to determine whether organ weights were affected by these parameters. In this study, reference ranges for organ weights are presented for Malaysian adult men and women.

Antioxidant Effects of Apocynum venetum Tea Extracts on d-Galactose-Induced Aging Model in Mice.

As a traditional Chinese medicinal drink, Apocynum venetum, a local tea from Xinjiang, China, is favored for its rich flavor and biological functionality. This study looked at aging mice induced by d-galactose to determine the in vivo anti-aging effect of Apocynum venetum tea extracts (AVTEs) and its bioactive components. We evaluated the weight of major organs (via organ index) and pathological changes in the liver. We also detailed the effects of AVTE (250 mg/kg in the low dose group, 500 mg/kg in the high dose group) on biochemical parameters (malondialdehyde, superoxide dismutase, glutathione, glutathione peroxidase, catalase, total antioxidant capacity, and nitric oxide) and cytokines (IL-6, IL-12, TNF-α and IL-1β) in the serum of aging mice. We investigated the anti-aging effects of AVTE in d-galactose-induced aging mice via quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR) assay. In addition, we analyzed the biological components of AVTEs by high performance liquid chromatography (HPLC). The results were remarkable, suggesting that AVTE significantly improved d-galactose-induced aging mice, with the high dose group showing the best results among other groups. ATVE can effectively alleviate hepatocyte edema, as well as inflammatory cell infiltration and injury in mice, induce a protective effect via up-regulation of glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) antioxidant related factors, and play an important role in the up-regulation of anti-inflammatory factors (IL-10) and the down-regulation of pro-inflammatory factors (IL-6, TNF-α and IL-1β). At the same time, HPLC analysis showed that AVTEs contain neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, rutin, isoquercitrin, isochlorogenic acid B, isochlorogenic acid A, astragalin, isochlorogenic acid C, rosmarinic acid, and trans-cinnamic acid. Thus, AVTE appears to be an effectively functional drink due to its rich functional components and anti-aging activities.

Safety of exposure to high static magnetic fields (2T-12T): a study on mice.

We aimed to evaluate the biological effects of high static magnetic field (HiSMF, 2-12Tesla [T]) exposure on mice in a stable and effective breeding environment in the chamber of a superconducting magnet. C57BL/6 mice were bred in the geomagnetic field and HiSMF with different magnetic field strengths (2-4T, 6-8T, and 10-12T) for 28days. The body weight, blood indices, organ coefficients, and histomorphology of major organs were analyzed. The results showed that the HiSMF had no significant effect on the body weight, organ coefficients, or histomorphology of major organs in mice. The HiSMF had no effect on most routine blood and biochemical indices, but the value of the mean corpuscular hemoglobin (MCH) was increased in the 2-4T group compared with that of the other groups, and the uric acid level (UA) was decreased in the three HiSMF groups compared with that of the control group. The C57BL/6 mice were not affected when they were exposed to different HiSMF environments for 28days. • No physiological problems were observed in mice with long-term whole-body exposure to HiSMF.

Therapeutic Effects of Melatonin in Lead-Induced Toxicity in Rats

Exposure to lead results in significant accumulation in most of vital organs, and free radical damage has been proposed as a cause of lead-induced tissue damage, where oxidative stress is a likely molecular mechanism. This study was designed to evaluate therapeutic effects of melatonin in lead-induced organ toxicity in rats. The therapeutic effects of melatonin on lead induced toxicity in rats were evaluated using 36 rats, which were allocated into 3 groups and treated as follows: Group I, includes 12 rats injected subcutaneously with 0.2 ml physiological saline for 30 days, followed by treatment with a daily dose of 20mg/kg melatonin, administrated I.P for the successive 30 days; groups II and III, each includes 12 rats , injected with lead acetate 100 mg/kg/day s.c for 30 days, followed by treatment with intraperotoneal injection of physiological saline (0.2 ml) or melatonin 20mg/kg/day for the next 30 days. At the end of treatment period, the rats were sacrificed by an overdose (100mg/kg) of thiopental (twenty-four hour after the last injection). Craniotomy and laparotomy were performed to obtain the brains, livers and kidneys for the assessment of tissue damage. The changes in total body weight, weight of major organs (brain, liver and kidney), oxidative stress parameters, hemoglobin content, liver and renal functions, and histological appearance of the studied organs were evaluated and compared with that of negative and positive controls. Treatment with melatonin reverses the damage induced by lead in many organs and tissues through the reduction of MDA levels in RBCs, brain, liver and kidney; increases GSH levels in all studied organs; in addition to the improvement in the indices of the functions of the organs studied. These findings demonstrated that melatonin is capable of reversing damage of rat tissues caused by successive doses of lead acetate, and animals had restored their organ functions due to treatment with melatonin.&#x0D; Key words: Melatonin, Lead poisoning, Oxidative stress

A moderate metal-binding hydrazone meets the criteria for a bioinorganic approach towards Parkinson's disease: Therapeutic potential, blood-brain barrier crossing evaluation and preliminary toxicological studies

Alzheimer's and Parkinson's diseases share similar amyloidogenic mechanisms, in which metal ions might play an important role. In this last neuropathy, misfolding and aggregation of α-synuclein (α-Syn) are crucial pathological events. A moderate metal-binding compound, namely, 8-hydroxyquinoline-2-carboxaldehyde isonicotinoyl hydrazone (INHHQ), which was previously reported as a potential ‘Metal-Protein Attenuating Compound’ for Alzheimer's treatment, is well-tolerated by healthy Wistar rats and does not alter their major organ weights, as well as the tissues' reduced glutathione and biometal levels, at a concentration of 200mgkg−1. INHHQ definitively crosses the blood-brain barrier and can be detected in the brain of rats so late as 24h after intraperitoneal administration. After 48h, brain clearance is complete. INHHQ is able to disrupt, in vitro, anomalous copper-α-Syn interactions, through a mechanism probably involving metal ions sequestering. This compound is non-toxic to H4 (human neuroglioma) cells and partially inhibits intracellular α-Syn oligomerization. INHHQ, thus, shows definite potential as a therapeutic agent against Parkinson's as well.

Oral toxicity of elephant foot yam (Amorphophallus paeoniifolius) tuber in mice

Context: Amorphophallus paeoniifolius tuber is an important constituent of Ayurvedic system of medicine. The tuber of this plant has high medicinal value and is consumed as a food. It is associated with acridity (itchy sensation in mouth and throat) upon oral consumption and presence of high oxalates raphides. Aims: To evaluate the acute and subacute oral toxicity studies of methanolic (APME) and aqueous (APAE) extracts of Amorphophallus paeoniifolius tuber in Swiss albino mice according to OECD guidelines. Methods: In acute oral toxicity study, the mice were orally administered a single dose of APME or APAE (2000 mg/kg) and clinical signs and mortality were observed for 14 days. In subacute (repeated dose) oral toxicity study, the mice were administered once daily, orally with APME or APAE (1000 mg/kg) up to 28 days. The parameters assessed were behavior, clinical signs, body weight, feed and water consumption, urinary, biochemical, hematological and major organ weights and histology. Results: In acute toxicity study, there was no treatment related mortality and morbidity in any of the group. In subacute toxicity study, there were no significant changes in behavior, body weight, feed and water consumption, urinary, biochemical, hematological and organ weight and histological parameters compared to vehicle treated group. There was no treatment related mortality or morbidity. Conclusions: Administration of methanolic and aqueous extracts of Amorphophallus paeoniifolius tuber, individually in acute and 28 days repeated dose in mice, did not exhibit any toxicity or adverse effect at the doses used.

Anti-inflammatory activity and acute toxicity studies of hydroalcoholic extract of Herissantia tiubae

Hydroalcoholic extract of aerial parts of Herissantia tiubae (K. Schum.) Brizicky, Malvaceae, was evaluated in experimental models of inflammation and toxicity. For toxicity assays, male and female Swiss mice were orally treated with hydroalcoholic extract of H. tiubae (2000mg/kg) and analyzed by consumption of water and food, body weight, mortality and rates of major organ weights, as well as biochemical and hematological indexes. For anti-inflammatory effect, phlogistic agents such as carrageenan or acetic acid were used to evaluate paw edema, cell migration and cytokine production. It was also investigated the hydroalcoholic extract of H. tiubae in RAW 264.7 macrophage lineage by nitric oxide and cytokine productions. Swiss mice treated with hydroalcoholic extract of H. tiubae showed low toxicity and (50 or 100mg/kg) was able to reduce significantly (p<0.01, p<0.001) polymorphonuclear cell migration, TNF-α and IL-1β production in the carrageenan-induced peritonitis. However the hydroalcoholic extract of H. tiubae (50, 100 or 200mg/kg) did not reduce carrageenan-induced paw edema. Additionally, hydroalcoholic extract of H. tiubae did not present cytotoxicity at concentrations of 6.25, 12.5, 25 or 50μg/ml but induced significantly decrease of NO, TNF-α and IL-6 production in macrophage lineage. This study suggests that hydroalcoholic extract of H. tiubae has anti-inflammatory activity by inhibiting cell migration mainly by decreasing the inflammatory cytokine levels at the inflamed site independently of the anti-edematogenic effect.